COVID-19 is a public health emergency that has rapidly spread to over 200 countries and regions, and no effective treatment has been established to date. Severe and critical cases have been associated with higher mortality due to acute respiratory distress syndrome (ARDS) and cytokine storm. Based on the novelty and recent emergence of COVID-19, no effective treatment regimen has been identified, thus prompting clinicians to engage in drug repurposing to address the immediate therapeutic need. This study focused on the molecular target angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 and screened a group of ACE2 agonists by bioinformatics. Glucocorticoids are a type of ACE2 activator. We verified the efficacy of nine chemicals on regulating ACE2 expression in human GES-1, an upper digestive tract epithelial cell line, and THP-1, a human monocyte cell line, and found that several glucocorticoids imparted activating effects on ACE2 in both cell lines. The drugs triciribine and kinetin riboside activate ACE2 expression or inhibit IL-6 production in macrophages to some extent. In addition, we compared the efficacies of several glucocorticoids. Hydrocortisone showed the strongest effect on ACE2 activation, followed by prednisolone, dexamethasone, and methylprednisolone. We retrospectively analyzed the therapeutic efficacy of nine severe or critical patients from a cohort of 90 COVID-19 cases, who received medium to small doses of glucocorticoids from our integrated medical team in Wuhan. Seven out of nine patients revealed significant improvement in clinical parameters and chest CT images. This study provides experimental and clinical evidence that medium-to-low-dose glucocorticoids may play a protective role in the respiratory and digestive systems by activating ACE2 and suppressing cytokine storm.

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Background: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. Methods: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. Results: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r ¼ 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. Conclusion:The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

Aims In patients with coronavirus disease 2019 (COVID‐19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model. Methods and results This retrospective cohort study included patients with confirmed COVID‐19 from Wuhan Tongji Hospital (Wuhan, China). Data were compared between those with and without myocardial injury. Kaplan–Meier analysis and Cox regression models were used to describe the association between myocardial injury and poor prognosis. Simple correlation analyses were used to find factors associated with high‐sensitivity cardiac troponin I levels. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with myocardial injury. The area under the receiver operating characteristic curve was used to determine the predictive value of the model. Of 353 patients included in the study, 79 presented myocardial injury. Patients with myocardial injury had higher levels of inflammation markers, poorer liver and kidney function, and more complications compared with patients without myocardial injury. High‐sensitivity cardiac troponin I levels were significantly associated with neutrophil/lymphocyte ratio, creatinine, d ‐dimer, lactate dehydrogenase, and inflammatory cytokines and negatively associated with oxygen saturation. It was significantly associated with poor prognosis after adjusting for age, sex, and complications. Multivariate regression showed that myocardial injury was associated with a high neutrophil/lymphocyte ratio (odds ratio 2.30, 95% CI 1.11–4.75, per standard deviation increase, P = 0.02), creatinine (3.58, 1.35–8.06, P = 0.01), and lactate dehydrogenase (3.39, 1.42–8.06, P = 0.01) levels. Using a predictive model, the area under the receiver operating characteristic curve was 0.92 (0.88–0.96). Conclusions In patients with COVID‐19, neutrophil/lymphocyte ratio, creatinine, and lactate dehydrogenase are blood markers that could help identify patients with a high risk of myocardial injury at an early stage.

γδ T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite γδ T cells’ origin in the thymus, detailed mechanisms regulating γδ T cell development remain poorly understood. N 6 -methyladenosine (m 6 A) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in γδ T cell biology is still unclear. Here, we show that depletion of the m 6 A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells, which confers enhanced protection against gastrointestinal Salmonella typhimurium infection. Mechanistically, loss of ALKBH5 favors the development of γδ T cell precursors by increasing the abundance of m 6 A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components Jagged1 and Notch2 . As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of γδ T cell precursors, leading to an expanded mature γδ T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m 6 A modification in the regulation of γδ T cell early development.

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Eight GST fusion proteins containing overlapping preS1 fragments were prepared successfully. They were used for the study on the immunogenic dom-ains in preS1 (21-119) region. The preS1 (34-59) fragments were the major immunogenic domains in the preS1 region, and the antibodies against these fragments were speculated to be virus-neutralizing. Therefore, the incorporation of preS1 (34-59) fragments into epitope-based HBV vaccines may be efficient for enhancement of immune response. Additionally, the results also imply that there are more complex immune responses to preS1 region and more abundant immunogenic domains in humans.